Intracellular nanovesicles mediate integrin trafficking during cell migration
Intracellular nanovesicles mediate integrin trafficking during cell migration
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细胞内纳米囊泡介导细胞迁移过程中的整合素运输
DOI：
10.1101/2020.08.19.257287
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Larocque G
中科院分区：
文献类型：
--
作者：
Larocque G
膜运输是通过细胞表面受体（例如整合素异二聚体）的内吞作用和再循环来调节细胞迁移的重要调节剂。细胞内纳米囊泡（INV）是最近发现的一类运输囊泡，参与包括回收途径在内的多个膜运输步骤。唯一已知的 INV 标记是肿瘤蛋白 D54 (TPD54/TPD52L2)，它是 TPD52 样蛋白家族的成员。癌症中 TPD52 样家族蛋白的过度表达与不良预后和侵袭性转移表型有关，这表明细胞迁移可能在这些条件下发生改变。在这里，我们表明 TPD54 通过其 C 末端保守的带正电基序直接结合高曲率膜来与 INV 结合。我们描述了 TPD52 样家族的其他成员如何与 INV 相关，并记录了所有 INV 的 Rab GTPase 补体。 TPD52 样蛋白的消耗会抑制细胞迁移和侵袭；我们发现这可能是由于整合素回收的改变造成的。我们的研究强调了 INV 参与细胞表面蛋白的运输，以产生对健康和疾病具有重要生物学意义的输出。
Membrane traffic is an important regulator of cell migration through the endocytosis and recycling of cell surface receptors such as integrin heterodimers. Intracellular nanovesicles (INVs), are a recently identified class of transport vesicle that are involved in multiple membrane trafficking steps including the recycling pathway. The only known marker for INVs is Tumor Protein D54 (TPD54/TPD52L2), a member of the TPD52-like protein family. Overexpression of TPD52-like family proteins in cancer has been linked to poor prognosis and an aggressive metastatic phenotype which suggests cell migration may be altered under these conditions. Here we show that TPD54 associates with INVs by directly binding high curvature membrane via a conserved positively charged motif in its C-terminus. We describe how other members of the TPD52-like family are also associated with INVs and we document the Rab GTPase complement of all INVs. Depletion of TPD52-like proteins inhibits cell migration and invasion; and we show that this is likely due to altered integrin recycling. Our study highlights the involvement of INVs in the trafficking of cell surface proteins to generate biologically important outputs in health and disease.